The purpose of this project is to elucidate the structure of the prosthetic heme adducts obtained during cytochrome P-450 metabolism of substrates such as ethylene, fluroxene, griseofulvin, dicarbethoxy-1, 4-dihydrocollidine, and 1-aminobenzotriazole. A parallel purpose is to determine the mechanisms of the interactions of these substrates with cytochrome P-450, the relationship between their structure and destructive activity, and their isoenzyme specificity. The structural work will be carried out primarily with the aid of field desorption mass spectrometry and high resolution NMR, in conjunction with a synthetic program. Kinetic studies of enzyme inactivation, using microsomal preparations and reconstituted pure enzymes, are to be performed.